Autoimmune risk variants in ERAP2 are associated with gene-expression levels in thymus

Abstract

Genetic polymorphisms in the endoplasmic reticulum aminopeptidase (ERAP)1 and ERAP2 genes have been associated with several autoimmune diseases (AIDs) at a genome-wide significance level. In this study, we performed a cis expression quantitative trait locus (eQTL) screen to investigate whether seven fine-mapped AID single-nucleotide polymorphisms (SNPs) in the ERAP-region influence the gene-expression levels of ERAP1 and ERAP2 in thymus. After quality control, we identified six significant eQTLs. We further assessed the peak eQTL signals, and both genes showed highly significant and independent thymic eQTL signals (P=2.16 × 10^-15 and P=8.22 × 10^-23, respectively). Interestingly, the peak eQTL signal overlapped with the AID risk loci in ERAP2 (r²>0.94), but were distinct in ERAP1 (r²<0.4). Finally, among the SNPs showing the most significant eQTL associations with ERAP2 (P<3.4 × 10^-20), six were located within transcription factor motifs in an enhancer region in thymus. Our study therefore reveals the fine-mapped AID risk variants that act as eQTLs with ERAP2 in thymus, and highlights the potential causal regulatory variants.